JC virus (JCV) is a causative agent of progressive multifocal leukoencephalopathy (PML) that occurs mainly in immunosuppressed patients, especially those with HIV/AIDS. JCV belongs to the Polyomavirus that are characterized by non-enveloped icosahedral capsids containing small, circular, double-stranded DNA genomes. JCV is widely distributed among the population world-wide. However, infections are usually restricted by the immune system. In this article we briefly provide an overview of the interaction between JCV and host immunity. We also review the biological and physical characteristics and the lifecycle, receptors interaction, intracellular trafficking, viral transcription and replication, progeny virus propagation of JCV to examine the pathogenicity mechanism of PML.